Impaired mast cell maturation and degranulation and attenuated allergic responses in Ndrg1-deficient mice

Yoshitaka Taketormi, Kohei Sunaga, Satoshi Tanaka, Masanori Nakamura, Satoru Arata, Tomohiko Okuda, Tae Chul Moon, Hyeun Wook Chang, Yukihiko Sugimoto, Koichi Kokame, Toshiyuki Miyata, Makoto Murakami, Ichiro Kudo

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40 Citations (Scopus)


We have previously reported that N-myc downstream regulated gene-1 (NDRG1) is an early inducible protein during the maturation of mouse bone marrow-derived mast cells (BMMCs) toward a connective tissue mast cell-like phenotype. To clarify the function of NDRG1 in mast cells and allergic responses, we herein analyzed mast cell-associated phenotypes of mice lacking the Ndrg1 gene. Allergic responses including IgE-mediated passive systemic and cutaneous anaphylactic reactions were markedly attenuated in Ndrg1-deficient mice as compared with those in wild-type mice. In Ndrg1-deficient mice, dermal and peritoneal mast cells were decreased in number and morphologically abnormal with impaired degranulating ability. Ex vivo, Ndrg1-deficient BMMCs cocultured with Swiss 3T3 fibroblasts in the presence of stem cell factor, a condition that facilitates the maturation of BMMCs toward a CTMC-like phenotype, displayed less exocytosis than replicate wild-type cells after the cross-linking of FcεRI or stimulation with compound 48/80, even though the exocytotic response of IL-3-maintained, immature BMMCs from both genotypes was comparable. Unlike degranulation, the production of leukotriene and cytokines by cocultured BMMCs was unaffected by NDRG1 deficiency. Taken together, the altered phenotypes of Ndrg1-deficient mast cells both in vivo and ex vivo suggest that NDRG1 has roles in the terminal maturation and elector function (degranulation) of mast cells.

Original languageEnglish
Pages (from-to)7042-7053
Number of pages12
JournalJournal of Immunology
Issue number11
Publication statusPublished - Jun 1 2007

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology


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